POTENTIALLY AMYLOIDOGENIC FRAGMENT OF 50 KDA AND INTRACELLULAR PROCESSING OF AMYLOID PRECURSOR PROTEIN IN CELLS CULTURED UNDER LEUPEPTIN

Citation
K. Tsuzuki et al., POTENTIALLY AMYLOIDOGENIC FRAGMENT OF 50 KDA AND INTRACELLULAR PROCESSING OF AMYLOID PRECURSOR PROTEIN IN CELLS CULTURED UNDER LEUPEPTIN, Brain research, 659(1-2), 1994, pp. 213-220
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0006-8993
Volume
659
Issue
1-2
Year of publication
1994
Pages
213 - 220
Database
ISI
SICI code
0006-8993(1994)659:1-2<213:PAFO5K>2.0.ZU;2-G
Abstract
The principal neuropathological feature of Alzheimer's disease is extr acellular deposition of similar to 4-kDa proteinous fragment, designat ed as beta-amyloid peptides (beta/A4 peptides) derived by proteolytic cleavage from amyloid precursor protein (APP), a large cell-surface re ceptor-like protein. There has been evidence that APP is proteolytical ly degraded in the secretory and endosomal/lysosomal pathways. The pat hway in which APP is cleaved to generate beta/A4 peptides is still not identified. To clarify the intracellular processing of APP into the g eneration of beta/A4 peptides, we detected and characterized potential ly amyloidogenic or non-amyloidogenic fragments using newly establishe d monoclonal and polyclonal antibodies in the cultured cells with or w ithout leupeptin, potent lysosomal protease inhibitor of lysosome. APP fragments of 50 and 20 kDa containing full-length beta/A4 peptides we re identified in the cultured cells. Immunoblot analysis, biochemical study for specific marker enzyme activity of the fractions obtained fr om subcellular fractionation, sucrose density gradient centrifugation indicated that the 50-kDa APP fragment was produced in the compartment closely related to endosomal/lysosomal system. Our data suggest that the endosomal/lysosomal pathway is involved in the processing and gene ration of beta/A4 peptides.